The overall goal of this work is to develop a novel monoclonal antibody for cancer therapy. HGF is a paracrine angiogenic factor and an autocrine growth factor for many different types of cancer cells. Thus antagonistic monoclonal antibodies to HGF are expected to have broad anti-cancer therapeutic potential. In this study, we will (1) characterize selected blocking anti-HGF monoclonal antibodies (mAbs) and generate better blocking mAbs; (2) demonstrate anti-tumor activities and anti-angiogenic activities of anti-HGF mAbs in vitro; and (3) demonstrate the inhibition of human tumor growth by anti-HGF mAbs in a xenograft nude mouse model. The PHASE II studies will include determination of the anti-tumor activities of one or more anti-HGF mAbs with a more extensive panel of human tumor cell lines in xenograft nude mouse model, including metastasis models, and in combination with standard chemotherapeutic agents. The effects of antibody dose and time of administration will be examined. The mechanism of action (apoptosis, necrosis, etc.) will also be investigated and preliminary observations of any toxicity will be made. In addition, we will reformat the most promising mAb as a mouse-human chimeric mAb and/or a humanized mAb to generate an agent suitable for clinical trials in human patients.